Mechanism driven structural elucidation of forced degradation products from hydrocortisone in solution.

Abstract:

:Hydrocortisone degradation products 1, 2, 3, and 4 along with hemiacetal derivatives 5, 6, 7, and 8 were observed through stressed hydrocortisone in solution. Their structures were identified based on HPLC-UV, HPLC-MS, and HPLC-HRMS (high resolution/high accuracy mass spectrometry) analyses as well as reaction mechanistic investigation and synthesis for structural confirmation. 1 and 2 are a pair of E/Z isomers and they were generated through acid catalyzed tautomerization/dehydration of hydrocortisone. Incorporation of water to 1 and 2 resulted in the formation of 3. We also discovered new degradation product 4 which was converted from 3 by oxidation. The degradation products were synthesized by stressing hydrocortisone under the optimized conditions and their structures were characterized by NMR ((1)H/(13)C, COSY, HMBC, HSQC, NOESY) and HRMS analyses. The degradation pathway of hydrocortisone is postulated.

journal_name

J Pharm Biomed Anal

authors

Zhang F,Zhou J,Shi Y,Tavlarakis P,Karaisz K

doi

10.1016/j.jpba.2016.06.004

subject

Has Abstract

pub_date

2016-09-05 00:00:00

pages

333-341

eissn

0731-7085

issn

1873-264X

pii

S0731-7085(16)30321-1

journal_volume

128

pub_type

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